Question: I had unsuccessful pituitary surgery and then had a bilateral adrenalectomy. I am feeling better, but have not been able to lose any weight. My maintenance dose is 37.5 mg per day of Cortef, which I understand is on the high end of replacement doses. My endocrinologist doesn’t think it is wise to decrease my replacement dose any further because of a concern about Nelson’s syndrome. Can keeping replacement doses higher than normal keep Nelson’s from occurring?

Answer: Following bilateral adrenalectomy, chronic treatment with steroids is essential and the objective is to replace the normal production of cortisol and aldosterone from the adrenal glands. The normal production of cortisol in humans is in the range of 12-25 mg each day and this needs to be increased 2-3 fold during episodes of acute stress or illness depending on severity of stress.

Hydrocortisone (Cortef) is the short-acting form of cortisol most frequently utilized for replacement as it is closest to what is produced naturally by the adrenal. However because it is short-lived in the body it needs to be taken as oral tablets in divided doses during the day to mimic normal production by the adrenal. Many patients get better results if the hydrocortisone is taken in three doses for example 10-15 mg at awakening, 5-10 mg in mid morning and 2.5 to 5 mg in mid afternoon. Total doses can vary from 15-30 mg per day.

Administering larger doses chronically could maintain or produce manifestations similar to Cushing’s syndrome with weight gain, skin bruising, muscle weakness and osteoporosis. Other glucocorticoids utilized have slightly longer duration of their effect: they can include cortisone acetate (37.5 mg of cortisone acetate is equivalent to 30 mg of hydrocortisone) or prednisone (7.5 mg of prednisone is equivalent to 30 mg of hydrocortisone).

In addition to hydrocortisone, patients usually require another steroid called fludrocortisone (Florinef) to replace the missing aldosterone and to maintain good balance of blood pressure, sodium and potassium levels in their body. The usual doses of fludrocortisone are in the range of 0.05 to 0.1 or 0.15 mg per day. These can be adjusted based on blood pressure and blood levels of potassium and renin.

Bilateral adrenalectomy is used only as a last solution for Cushing’s disease when the pituitary tumor responsible for over production of ACTH and of cortisol cannot be removed completely by pituitary surgery. If residual pituitary tumor is detectable radiologically and cannot be surgically removed, radiotherapy or radiosurgery can be utilized in some patients depending on localization and size of tumor, while cortisol production is controlled by medications which inhibit steroid production such as ketoconazole. Bilateral adrenalectomy would not be performed unless radiotherapy is found to be without success after 2-3 years of evaluation. In some patients with Cushing’s disease not cured by pituitary surgery or in whom disease relapse occurs after a few years of improvement, and the residual pituitary tumor is not detectable by MRI, then bilateral adrenalectomy may be preferable to radiotherapy.

The name of Nelson’s syndrome is used when the pituitary tumor increases in size following bilateral adrenalectomy and is accompanied by further large increases in ACTH levels in blood. This was found to occur in different studies in 8 to 29% after bilateral adrenalectomy. Close monitoring by regular MRI scans and plasma ACTH levels (3-6 months after adrenalectomy and yearly afterwards) should be conducted to detect progression of the residual pituitary tumor. In the event of tumor progression, repeat pituitary surgery or radiotherapy may become necessary. Routine preventive radiotherapy after bilateral adrenalectomy is not generally recommended, unless a relatively large non-resectable tumor is present. There is no indication that maintaining an excess dose of replacement with hydrocortisone or other glucocorticoids would prevent the development of Nelson’s syndrome. However maintaining excess cortisone replacement chronically can definitively produce the deleterious symptoms and complications of Cushing’s syndrome and should be avoided.

By Dr. Andre Lacroix MD (Winter, 2009)